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  • Title: Pioglitazone-induced body weight gain is prevented by combined administration with the lipoprotein lipase activator NO-1886.
    Author: Kusunoki M, Tsutsumi K, Sato D, Nakamura A, Habu S, Mori Y, Morishita M, Yonemoto T, Miyata T, Nakaya Y, Nakamura T.
    Journal: Eur J Pharmacol; 2011 Oct 15; 668(3):486-91. PubMed ID: 21835171.
    Abstract:
    Pioglitazone improves insulin resistance in diabetics but often causes body weight gain. The lipoprotein lipase activator NO-1886 has been shown to exert both anti-obesity and anti-insulin-resistance effects. In this study, we investigated the effect of the combined administration of pioglitazone with NO-1886 (pioglitazone+NO-1886) in preventing body weight gain in insulin-resistant, high-fat fed rats. The rats were fed a standard or high-fat diet for 16 weeks. The high-fat fed rats were randomized at week 9 into 4 groups (i.e., control, pioglitazone (30 mg/kg/day), NO-1886 (100mg/kg/day), and pioglitazone+NO-1886 (30 and 100mg/kg/day, respectively)). The high-fat fed control rats developed obesity and insulin resistance. After 7 weeks of drug treatment, pioglitazone+NO-1886 was found to prevent the body weight gain caused by pioglitazone alone (pioglitazone+NO-1886: Δ76.0 ± 16.8 g vs. pioglitazone: Δ127.8 ± 39.5 g, P<0.05) and to increase glucose infusion rate during insulin clamp, compared with the results in the high-fat fed control group. No differences in plasma nonesterified fatty acid, leptin, adiponectin, glucose, or insulin levels were observed between the pioglitazone+NO-1886 and the pioglitazone-alone groups. However, plasma total cholesterol and HDL-cholesterol levels were significantly increased and plasma triglyceride levels were slightly decreased in the pioglitazone+NO-1886 group, compared with the values in the pioglitazone-alone group. In summary, the combined administration of pioglitazone and NO-1886 prevented the pioglitazone-induced body weight gains and ameliorated insulin resistance observed in high-fat fed rats. These results indicate that combined therapy with pioglitazone and NO-1886 may be beneficial for the treatment of type 2 diabetes.
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